We are studying the relationship between membrane structure and function. The membrane systems we use range from simple model membrane vesicles to membranes which envelope animal viruses and eucaryotic cells. We are using several methods to monitor the structure of membranes, e.g., electron spin resonance spectroscopy (ESR), cross-linking reagents and photoreactive probes. Our goal is to answer questions such as: 1) What are the dynamics of association between the subunits of cholera toxin and the target cell membrane? 2) What is the nature of the interaction between membranes and the individual proteins which comprise the lytic complex of complement (C5b-9); and 3) What role do membranes play in the immune response? We have recently synthesized several amphiphilic derivatives of ESR probes, photoactivable probes, and antigens haptens which will insert spontaneously into both artificial and biological membranes. These amphiphilic molecules penetrate the outer surface of the membrane bilayer but are restricted in their ability of flip across to the inner surface. Such molecules permit us to monitor the physical properties of a single surface monolayer of sealed membrane vesicle preparations, to radiolabel proteins which inhabit or insert into a specific monolayer and to modify the surface informational content of the cell at will. Consequently, while we are interested in the physical state of the membrane, we are also in an excellent position strategy-wise to map the position of integral membrane proteins and to initiate cell surface engineering experiments which will undoubtedly have enormous ramifications in the area of cell-cell recognition.